KCNQ1 variants associate with hypertension in type 2 diabetes and affect smooth muscle contractility in vitro

被引:5
作者
Huang, Kuo-Chin [1 ,2 ]
Li, Te-Mao [1 ]
Liu, Xiang [3 ]
Chen, Jin-Hua [4 ,5 ,6 ,7 ]
Chien, Wen-Kuei [8 ]
Shiao, Yi-Tzone [9 ]
Tsang, Hsinyi [3 ]
Lin, Ting-Hsu [10 ]
Liao, Chiu-Chu [10 ]
Huang, Shao-Mei [10 ]
Li, Ju-Pi [1 ,11 ]
Lin, Cheng-Wen [12 ]
Lin, Jung-Chun [13 ]
Lin, Chih-Chien [14 ]
Lai, Chih-Ho [15 ]
Cheng, Chi-Fung [16 ]
Liang, Wen-Miin [16 ]
Hung, Chien-Hui [17 ]
Chen, Ching-Chu [1 ,18 ]
Lin, Ying-Ju [1 ,10 ]
Tsai, Fuu-Jen [1 ,10 ,19 ]
机构
[1] China Med Univ, Sch Chinese Med, Taichung, Taiwan
[2] China Med Univ Hosp, Dept Integrat Tradit Chinese & Western Med, Taichung, Taiwan
[3] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA
[4] China Med Univ, Biostat Ctr, Taichung, Taiwan
[5] China Med Univ, Sch Publ Hlth, Taichung, Taiwan
[6] Taipei Med Univ, Biostat Ctr, Taipei, Taiwan
[7] Taipei Med Univ, Sch Publ Hlth, Taipei, Taiwan
[8] Natl Ctr High Performance Comp, Natl Appl Res Labs, Hsinchu, Taiwan
[9] China Med Univ Hosp, Ctr Heart, Taichung, Taiwan
[10] China Med Univ Hosp, Genet Ctr, Dept Med Res, Taichung, Taiwan
[11] China Med Univ Hosp, Rheumatism Res Ctr, Taichung, Taiwan
[12] China Med Univ, Dept Med Lab Sci & Biotechnol, Taichung, Taiwan
[13] Taipei Med Univ, Coll Med Sci & Technol, Sch Med Lab Sci & Biotechnol, Taipei, Taiwan
[14] Providence Univ, Dept Cosmet Sci, Taichung, Taiwan
[15] Chang Gung Univ, Dept Microbiol & Immunol, Taoyuan, Taiwan
[16] China Med Univ, Sch Publ Hlth, Grad Inst Biostat, Taichung, Taiwan
[17] Chang Gung Univ, Grad Inst Clin Med Sci, Taipei, Taiwan
[18] China Med Univ Hosp, Dept Med, Div Endocrinol & Metab, Taichung, Taiwan
[19] Asia Univ, Taichung, Taiwan
关键词
genetic variants; hypertension; KCNQ1; muscle contractility; type; 2; diabetes; INSULIN-RESISTANCE; OLDER PATIENTS; FOLLOW-UP; MELLITUS; CHANNELS; OBESITY; SUSCEPTIBILITY; COMPLICATIONS; RELEASE; ADULTS;
D O I
10.1002/jcp.25775
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
KCNQ1 encodes a potassium voltage-gated channel and represents a susceptibility locus for type 2 diabetes mellitus (T2DM). Here, we explored the association between KCNQ1 polymorphisms and hypertension risk in individuals with T2DM, as well as the role of KCNQ1 in vascular smooth muscle cell contraction in vitro. To investigate the relationship between KCNQ1 and the risk of developing hypertension in patients with T2DM, we divided the T2DM cohort into hypertension (n = 452) and non-hypertension (n = 541) groups. The Mann-Whitney U test, chi-square test, and multivariate regression analyses were used to assess the clinical characteristics and genotypic frequencies. In vitro studies utilized the rat aortic smooth muscle A10 cell line. Patients in the hypertension group were significantly older at the time of enrollment and had higher levels of body mass index, waist-to-hip ratio, and triglyceride than those in the non-hypertension group. The KCNQ1 rs3864884 and rs12576239 genetic variants were associated with hypertension in T2DM. KCNQ1 expression was lower in the individuals with the CC versus the CT and TT genotypes. Smooth muscle cell contractility was inhibited by treatment with a KCNQ1 inhibitor. These results suggest that KCNQ1 might be associated with hypertension in individuals with T2DM.
引用
收藏
页码:3309 / 3316
页数:8
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